肿瘤坏死因子样凋亡的微弱诱导剂在类风湿关节炎成纤维样滑膜细胞的表达

The expression of TWEAKR/Fn14 in Rheumatoid arthritis fibroblast-like synoviocytes

目的:通过对影响肿瘤坏死因子样凋亡的微弱诱导剂(TWEAKR/Fn14)在类风湿关节炎成纤维样滑膜细胞(RAFLS)表达因素的研究,探讨TWEAK诱导RAFLS活化及导致关节炎性破坏的相关机制。方法:将rhTWEAK与FLS共培养,同时加入TNF-α或IL-1β,应用免疫组化法定位检测TWEAKR/Fn14在RAFLS的表达,应用Western blot半定量检测TWEAKR/Fn14在RAFLS的表达。应用反转录-聚合酶链反应检测fn14基因mRNA的表达。结果:TWEAKR/Fn14表达在RAFLS的胞膜及胞质内,100μg/L的TWEAK增加TWEAKR/Fn14在RAFLS的表达及fn14mRNA的表达,TNF-α和IL-1β能够显著增强TWEAK对RAFLS的诱导作用。结论:RAFLS的质膜存在TWEAKR/Fn14表达,在重组TWEAK存在时TWEAKR/Fn14表达增加;TNF-α和IL-1β通过增加RAFLS的TWEAKR/Fn14表达,发挥对TWEAK生物学活性的协同作用。

AIM：To investigate the mechanism of TWEAK on Rheumatoid arthritis fibroblast-like synoviocytes （RA FLS） activation and articular destruction by analyzing expression of TWEAKR/Fn14 on RA FLS. METHODS： FLS was co-cultured with rhTWEAK, with TNF-α or IL-1β as a synergistic stimulator. Expression of TWEAKR/Fn14 protein on RA FLS was detected by Immunocytochemistry and Western blotting. The fn14 mRNA was measured by RT-PCR. RESULTS： TWEAKR/Fn14 was expressed on the cell membrane and in the cytoplasm of RA FLS. TWEAKR/Fn14 mRNA and protein induced by 100 μg/L TWEAK were higher than the control group. TNF-α and IL-1β had synergistic effect on expression of TWEAKR/Fn14 in RA FLS. CONCLUSION： TWEAKR/Fn14 was expressed on the cell membrane and in the cytoplasm of RA FLS, and recombinant TWEAK further enhanced the TWEAKR/Fn14 expression. TNF-α and IL-1β had synergistic effect on the biological activity of TWEAK by increasing the expression of TWEAKR/Fn14 on RA FLS.